Glutamate metabolism of the heart during coronary artery bypass grafting

Pietersen, Henk G.; Langenberg, C.J.M.; Geskes, Gijs; Soeters, Peter B.; Wagenmakers, Anton J. M.

doi:10.1016/s0261-5614(98)80308-7

Cited by 15 publications

(7 citation statements)

References 6 publications

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“…Here, metabolomic profiling indicates that HF patients have altered plasma metabolomic profiles, with a distinct panel of representative metabolites of lipid, amino acid, and nucleotide metabolism and mitochondrial Krebs cycle–associated substrates such as succinate and glutamate. Most altered in HF patients were the reduced level of succinate and the increased level of glutamate, the indicators of mitochondrial dysfunction and metabolic remodeling 45 . The lower succinate level suggests decreased concentration of Krebs cycle intermediates, which are critical for burning fats and carbohydrates 45, 46 .…”

Section: Discussionmentioning

confidence: 99%

“…Most altered in HF patients were the reduced level of succinate and the increased level of glutamate, the indicators of mitochondrial dysfunction and metabolic remodeling 45 . The lower succinate level suggests decreased concentration of Krebs cycle intermediates, which are critical for burning fats and carbohydrates 45, 46 . Diminished substrate metabolism is also indicated by changes in the succinate/glutamate and citrate/glutamate ratios, which were significantly decreased in HF.…”

Section: Discussionmentioning

confidence: 99%

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Cardiac Resynchronization Therapy Induces Adaptive Metabolic Transitions in the Metabolomic Profile of Heart Failure

Nemutlu

Zhang

et al. 2015

Journal of Cardiac Failure

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Background Heart failure (HF) is associated with ventricular dyssynchrony and energetic inefficiency, which can be alleviated by cardiac resynchronization therapy (CRT). The aim of this study was to determine the metabolomic signature in HF and its prognostic value for the response to CRT. Methods This prospective study consisted of 24 patients undergoing CRT for advanced HF and 10 control patients who underwent catheter ablation for supraventricular arrhythmia but not CRT. Blood samples were collected before and 3 months after CRT. Metabolomic profiling of plasma samples was performed using gas chromatography–mass spectrometry and nuclear magnetic resonance. Results The plasma metabolomic profile was altered in the HF patients, with a distinct panel of metabolites, including Krebs cycle and lipid, amino acid, and nucleotide metabolism. CRT improved the metabolic profile. The succinate/glutamate ratio, an index of Krebs cycle activity, improved from 0.58±0.13 to 2.84±0.60 (P<.05). The glucose/palmitate ratio, an indicator of the balance between glycolytic and fatty acid metabolism, increased from 0.96±0.05 to 1.54±0.09 (P<.01). Compared with the nonresponders to CRT, the responders had a distinct baseline plasma metabolomic profile, including higher isoleucine, phenylalanine, leucine, glucose, and valine levels and lower glutamate levels at baseline (P<.05). Conclusion CRT improves plasma metabolomic profile of HF patients indicating harmonization of myocardial energy substrate metabolism. CRT responders may have a favorable metabolic profile as a potential biomarker for predicting CRT outcome.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cardiac Resynchronization Therapy Induces Adaptive Metabolic Transitions in the Metabolomic Profile of Heart Failure

Nemutlu

Zhang

et al. 2015

Journal of Cardiac Failure

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“…It is known that approximately 85% of glutamate infused is taken up by the heart and is used in the synthesis of Krebs-cycle intermediates (16). It seems that our amino acid additive led to a conceivable enhancement of the oxidation.…”

Section: Effects Of Gik and Glutamine On Cardiac Metabolismmentioning

confidence: 93%

“…Metabolic support with amino acids, i.e. glutamate to replenish the intermediates in the citric acid cycle has also been suggested (11,15,16). Glutamate shortage has been observed after coronary surgery (11) and glutamic acid added to blood cardioplegia improves the ATP conservation in the human myocardium (15,17).…”

mentioning

confidence: 99%

Both Glucose-Insulin-Potassium and Glutamine in Warm Blood Cardioplegia Increase the Rates of Myocardial Glucose and Free Fatty Acid Oxidation

Elvenes

Korvald

Irtun

et al. 2002

Scandinavian Cardiovascular Journal

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“…The CABG procedure also leads to a substantial fall in the myocardial glutamate concentration in humans [18]. In a pilot study using isotopically labelled ["&N]-and ["$C]glutamate [19], we recently obtained evidence that the main fate of glutamate extracted by the human heart is a quantitative conversion into tricarboxylic acid cycle intermediates. Together these data seem to suggest that intravenous glutamate infusion potentially may improve cardiac performance following CABG surgery, via a more rapid recovery of the substrate flux through the tricarboxylic acid cycle and an increased contribution of the respiratory chain to cellular ATP production.…”

Section: Introductionmentioning

confidence: 99%

The effect of glutamate infusion on cardiac performance is independent of changes in metabolism in patients undergoing routine coronary artery bypass surgery

et al. 2001

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In a double-blind randomized placebo-controlled study, the effects of intravenous glutamate infusion on myocardial haemodynamics and metabolism were studied in 22 patients undergoing routine coronary artery bypass graft (CABG) surgery. Immediately after aortic cross-clamp release, an intravenous infusion of a solution of glutamate (125 mmol x l(-1)) at a rate of 1.5 ml x h(-1) x kg(-1) was given over 1 h to 11 patients (G group). The other 11 patients received a placebo infusion (0.9% NaCl) (P group). Haemodynamic functions and rates of exchange of glucose, non-esterified fatty acids and lactic acid over the heart were measured before sternotomy (T1), 40 min after cross-clamp release (T2) and 4 h after cross-clamp release (T3). At T2, decreases were seen in comparison with T1 in systemic vascular resistance index, and increases were seen in cardiac index and coronary sinus flow. All of these changes were greater in the G group than in the P group (P<0.05). Myocardial glutamate consumption increased 2-fold after glutamate administration. No significant changes were observed in the myocardial utilization of glucose, lactate or non-esterified fatty acids between the P and the G groups at T1, T2 or T3. These data show that an intravenous glutamate infusion after routine CABG surgery significantly improved cardiac haemodynamic performance without direct effects on cardiac substrate metabolism. This suggests that a reduction of the afterload via a peripheral vasodilatory effect is the main mechanism leading to the observed changes in haemodynamics. Earlier claims that patients with post-operative cardiac failure show metabolic benefits from the glutamate infusion do not seem to apply to patients undergoing routine CABG surgery.

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Glutamate metabolism of the heart during coronary artery bypass grafting

Cited by 15 publications

References 6 publications

Cardiac Resynchronization Therapy Induces Adaptive Metabolic Transitions in the Metabolomic Profile of Heart Failure

Cardiac Resynchronization Therapy Induces Adaptive Metabolic Transitions in the Metabolomic Profile of Heart Failure

Both Glucose-Insulin-Potassium and Glutamine in Warm Blood Cardioplegia Increase the Rates of Myocardial Glucose and Free Fatty Acid Oxidation

The effect of glutamate infusion on cardiac performance is independent of changes in metabolism in patients undergoing routine coronary artery bypass surgery

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